Does acute tryptophan depletion affect peripheral serotonin metabolism in the intestine?

D. Keszthelyi, F.J. Troost, D.M. Jonkers, E.L. van Donkelaar, J. Dekker, W.A. Buurman, A.A. Masclee

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Abstract

Background: Serotonin (5-hydroxytryptamine; 5-HT), a tryptophan metabolite, plays an important regulatory role in the human central nervous system and in the gastrointestinal tract. Acute tryptophan depletion (ATD) is currently the most widely established method to investigate 5-HT metabolism. Objective: The aim of this study was to assess the effect of an acute decrease in the systemic availability of tryptophan on intestinal 5-HT metabolism and permeability. Design: Thirty-three healthy volunteers (17 with ATD, 3 of whom dropped out; 16 placebo) participated in this randomized placebo-controlled study. Plasma and duodenal mucosal concentrations of 5-HT, 5-hydroxyindoleacetic acid (5-HIAA), and kynurenic acid (KA) were measured by HPLC-mass spectrometry. Intestinal barrier function was assessed with a multisugar plasma test, and analysis of tight junction transcription was performed in duodenal biopsy samples obtained by gastroduodenoscopy. Results: Mucosal 5-HT, 5-HIAA, and KA concentrations remained unaltered by ATD. In contrast, ATD significantly decreased plasma 5-HT (P <0.05) and 5-HIAA (P <0.0001) concentrations. After endoscopy, a significant increase in plasma 5-HT concentrations was observed in the placebo group (P = 0.029) compared with the ATD group. Moreover, a significant increase in plasma KA concentrations over time was found in the placebo group (P <0.05). No changes in intestinal barrier function were observed. Conclusions: An acute decrease in precursor availability does not affect mucosal concentrations of serotonergic metabolites, in contrast with systemic concentrations. ATD alters biochemical responses to acute stress from the endoscopic examination reflected by lower 5-HT concentrations. Changes in 5-HT concentrations were paralleled by alterations in KA concentrations, which suggest competition between the 2 metabolic pathways for the mutual precursor. This trial was registered at clinicaltrials.gov as NCT00731003. Am J Clin Nutr 2012;95:603-8.
Original languageEnglish
Pages (from-to)603-608
JournalAmerican Journal of Clinical Nutrition
Volume95
Issue number3
DOIs
Publication statusPublished - 2012

Fingerprint

Tryptophan
Intestines
Serotonin
Kynurenic Acid
Hydroxyindoleacetic Acid
Placebos
Tight Junctions
Metabolic Networks and Pathways
Endoscopy
Gastrointestinal Tract
Permeability
Mass Spectrometry
Healthy Volunteers
Central Nervous System
High Pressure Liquid Chromatography
Biopsy

Keywords

  • 5-hydroxyindoleacetic acid
  • gastrointestinal-tract
  • cerebrospinal-fluid
  • brain
  • permeability
  • depression
  • cortisol
  • reuptake
  • humans
  • lumbar

Cite this

Keszthelyi, D., Troost, F. J., Jonkers, D. M., van Donkelaar, E. L., Dekker, J., Buurman, W. A., & Masclee, A. A. (2012). Does acute tryptophan depletion affect peripheral serotonin metabolism in the intestine? American Journal of Clinical Nutrition, 95(3), 603-608. https://doi.org/10.3945/ajcn.111.028589
Keszthelyi, D. ; Troost, F.J. ; Jonkers, D.M. ; van Donkelaar, E.L. ; Dekker, J. ; Buurman, W.A. ; Masclee, A.A. / Does acute tryptophan depletion affect peripheral serotonin metabolism in the intestine?. In: American Journal of Clinical Nutrition. 2012 ; Vol. 95, No. 3. pp. 603-608.
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Keszthelyi, D, Troost, FJ, Jonkers, DM, van Donkelaar, EL, Dekker, J, Buurman, WA & Masclee, AA 2012, 'Does acute tryptophan depletion affect peripheral serotonin metabolism in the intestine?' American Journal of Clinical Nutrition, vol. 95, no. 3, pp. 603-608. https://doi.org/10.3945/ajcn.111.028589

Does acute tryptophan depletion affect peripheral serotonin metabolism in the intestine? / Keszthelyi, D.; Troost, F.J.; Jonkers, D.M.; van Donkelaar, E.L.; Dekker, J.; Buurman, W.A.; Masclee, A.A.

In: American Journal of Clinical Nutrition, Vol. 95, No. 3, 2012, p. 603-608.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Does acute tryptophan depletion affect peripheral serotonin metabolism in the intestine?

AU - Keszthelyi, D.

AU - Troost, F.J.

AU - Jonkers, D.M.

AU - van Donkelaar, E.L.

AU - Dekker, J.

AU - Buurman, W.A.

AU - Masclee, A.A.

N1 - WOS:000300638700011

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N2 - Background: Serotonin (5-hydroxytryptamine; 5-HT), a tryptophan metabolite, plays an important regulatory role in the human central nervous system and in the gastrointestinal tract. Acute tryptophan depletion (ATD) is currently the most widely established method to investigate 5-HT metabolism. Objective: The aim of this study was to assess the effect of an acute decrease in the systemic availability of tryptophan on intestinal 5-HT metabolism and permeability. Design: Thirty-three healthy volunteers (17 with ATD, 3 of whom dropped out; 16 placebo) participated in this randomized placebo-controlled study. Plasma and duodenal mucosal concentrations of 5-HT, 5-hydroxyindoleacetic acid (5-HIAA), and kynurenic acid (KA) were measured by HPLC-mass spectrometry. Intestinal barrier function was assessed with a multisugar plasma test, and analysis of tight junction transcription was performed in duodenal biopsy samples obtained by gastroduodenoscopy. Results: Mucosal 5-HT, 5-HIAA, and KA concentrations remained unaltered by ATD. In contrast, ATD significantly decreased plasma 5-HT (P <0.05) and 5-HIAA (P <0.0001) concentrations. After endoscopy, a significant increase in plasma 5-HT concentrations was observed in the placebo group (P = 0.029) compared with the ATD group. Moreover, a significant increase in plasma KA concentrations over time was found in the placebo group (P <0.05). No changes in intestinal barrier function were observed. Conclusions: An acute decrease in precursor availability does not affect mucosal concentrations of serotonergic metabolites, in contrast with systemic concentrations. ATD alters biochemical responses to acute stress from the endoscopic examination reflected by lower 5-HT concentrations. Changes in 5-HT concentrations were paralleled by alterations in KA concentrations, which suggest competition between the 2 metabolic pathways for the mutual precursor. This trial was registered at clinicaltrials.gov as NCT00731003. Am J Clin Nutr 2012;95:603-8.

AB - Background: Serotonin (5-hydroxytryptamine; 5-HT), a tryptophan metabolite, plays an important regulatory role in the human central nervous system and in the gastrointestinal tract. Acute tryptophan depletion (ATD) is currently the most widely established method to investigate 5-HT metabolism. Objective: The aim of this study was to assess the effect of an acute decrease in the systemic availability of tryptophan on intestinal 5-HT metabolism and permeability. Design: Thirty-three healthy volunteers (17 with ATD, 3 of whom dropped out; 16 placebo) participated in this randomized placebo-controlled study. Plasma and duodenal mucosal concentrations of 5-HT, 5-hydroxyindoleacetic acid (5-HIAA), and kynurenic acid (KA) were measured by HPLC-mass spectrometry. Intestinal barrier function was assessed with a multisugar plasma test, and analysis of tight junction transcription was performed in duodenal biopsy samples obtained by gastroduodenoscopy. Results: Mucosal 5-HT, 5-HIAA, and KA concentrations remained unaltered by ATD. In contrast, ATD significantly decreased plasma 5-HT (P <0.05) and 5-HIAA (P <0.0001) concentrations. After endoscopy, a significant increase in plasma 5-HT concentrations was observed in the placebo group (P = 0.029) compared with the ATD group. Moreover, a significant increase in plasma KA concentrations over time was found in the placebo group (P <0.05). No changes in intestinal barrier function were observed. Conclusions: An acute decrease in precursor availability does not affect mucosal concentrations of serotonergic metabolites, in contrast with systemic concentrations. ATD alters biochemical responses to acute stress from the endoscopic examination reflected by lower 5-HT concentrations. Changes in 5-HT concentrations were paralleled by alterations in KA concentrations, which suggest competition between the 2 metabolic pathways for the mutual precursor. This trial was registered at clinicaltrials.gov as NCT00731003. Am J Clin Nutr 2012;95:603-8.

KW - 5-hydroxyindoleacetic acid

KW - gastrointestinal-tract

KW - cerebrospinal-fluid

KW - brain

KW - permeability

KW - depression

KW - cortisol

KW - reuptake

KW - humans

KW - lumbar

U2 - 10.3945/ajcn.111.028589

DO - 10.3945/ajcn.111.028589

M3 - Article

VL - 95

SP - 603

EP - 608

JO - American Journal of Clinical Nutrition

JF - American Journal of Clinical Nutrition

SN - 0002-9165

IS - 3

ER -